Differential expression pattern and functioning of CD80 and CD86 in Th1 and Th2 immune responses induced by immunogenic drugs

Abstract

Rationale Immunogenic drugs, of which some are known to induce hypersensitivity reactions in man, may induce Th1- or Th2-associated immune responses. Here, we study the kinetics of the expression patterns and the functional importance of costimulatory activation markers in drug-induced Th1 or Th2 immune responses. Methods Data was acquired with the popliteal lymph node assay (PLNA) using bystander antigens. BALB/c mice were s.c. injected with Streptozotocin (STZ; inducing Th1 responses) or D-Penicillamine (D-Pen; inducing Th2 responses) in the hind footpad and some groups received additional i.p. treatment with anti-CD80, anti-CD86 or a combination of both MoAb. Additionally, we exposed CD80/CD86-deficient mice to either D-Pen or STZ. We measured the numbers of Ab secreting cells, production of IL-4, IFN-γ and TNF-α, and shifts in cell subtypes. Results In Th2 responses the expression of CD86, but not CD80, was increased and abrogation of the CD80/CD86 pathway inhibited the activation of lymphocytes, IL-4, IFN-γ, IgM and IgG1 secretion. In the Th1 response, both CD80 and CD86 were increased and abrogation of CD80/CD86 signaling caused no change in macrophage numbers and levels of IgG2a and IFN-γ, and in fact increased TNF-α and IgM secretion. Conclusions Th1- and Th2-inducing immunogenic drugs give rise to distinct profiles of cytokines, shifts in cell subtypes and expression patterns of CD80 and CD86. Additionally, ligation of CD80 and CD86 is indisputably required in the induction of D-Pen-induced Th2 responses, but seems to inhibit STZ-induced Th1 phenomena.